TXR
No.
012358
DATE:
October
20,
1997
MEMORANDUM
SUBJECT:
IMIDACLOPRID
­
Addendum
to
the
Report
of
the
Hazard
Identification
Assessment
Review
Committee.

FROM:
Jess
Rowland,
Branch
Senior
Scientist,
Science
Analysis
Branch,
Health
Effects
Division
(
7509C)

THROUGH:
K.
Clark
Swentzel,
Chairman,
Hazard
Identification
Assessment
Review
Committee
Toxicology
Branch
II,
Health
Effects
Division
(
7509C)

TO:
Richard
Loranger,
Branch
Senior
Scientist
Registration
Action
Branch,
Health
Effects
Division
(
7509C)

On
September
11,
1997,
the
Health
Effects
Division's
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
met
to
evaluate
the
toxicology
data
base
of
Imidacloprid
to
select
toxicological
endpoints
for
acute
dietary
as
well
as
occupational
and
residential
exposure
risk
assessments.
At
that
meeting
the
HIRC
concluded
that
dermal
risk
assessment
for
occupational
and
residential
exposures
are
not
required
based
on
the
lack
of
dermal
and
systemic
toxicity
following
single
and
repeated
exposures
to
Imidacloprid
in
laboratory
animals
and
thus,
there
is
no
concern
for
exposure
via
this
route.

On
September
15,
1997,
the
Risk
Assessment
Committee
(
RARC)
during
its
review
of
the
risk
assessment
document
for
Imidacloprid
raised
the
concern
as
to
why
the
neurotoxicity
endpoint,
which
was
identified
for
the
Acute
Dietary
exposure
was
not
selected
for
dermal
occupational/
residential
risk
assessments
as
well.

On
October
16,
1997,
HIARC
met
to
clarify
the
above
concern
raised
by
RARC.
The
HIARC's
conclusions
are
as
follows:
The
HIARC
concluded
that
the
neurotoxicity
endpoint,
although
applicable
for
Acute
Dietary
risk
assessment
is
not
appropriate
for
dermal
risk
assessments
for
the
following
reasons:

1).
The
clinical
signs
that
manifested
as
decreased
motor
activity
in
rats
following
a
single
oral
dose
at
42
mg/
kg/
day
was
observed
only
in
the
Acute
Neurotoxicity
Study
(
MRID
No.
43170301
&
43285801)
and
was
not
substantiated
in
other
studies
via
the
oral
or
the
dermal
routes.

2)
In
a
subchronic
toxicity
study,
no
neurotoxic
clinical
signs
or
neuropathology
were
seen
in
rats
following
repeated
oral
administrations
at
doses
of
0,
10.5,
69.3,
or
213
mg/
kg/
day
for
13
weeks.
For
neurotoxicity,
the
NOEL
was
>
213
mg/
kg/
day
(
MRID
No.
43286401).

3)
Although
neurotoxic
clinical
signs
observable
via
the
oral
route
are
also
observable
via
the
dermal
route,
no
such
neurotoxic
clinical
signs
were
observed
either
after
a
single
dermal
dose
in
the
Acute
Dermal
LD50
study
with
rats
(
MRID
No.
42055332)
or
after
repeated
dermal
applications
in
the
21­
Day
Dermal
Toxicity
with
rabbits
(
MRID
No.
42256329).

4)
The
lack
of
dermal
or
systemic
toxicity
at
the
Limit­
Dose
(
1000
mg/
kg/
day)
in
the
21­
Day
Dermal
Toxicity
indicate
poor
dermal
absorption
which
was
also
substantiated
by
the
lack
of
dermal
or
systemic
toxicity
in
the
Acute
Dermal
study
where
the
LD50
was
>
5000
mg/
kg/
day
(
MRID
Nos.
42055332
&
42256329)

5)
Poor
dermal
absorption
was
also
indicated
by
the
ratio
obtained
when
the
oral
NOEL
of
24
mg/
kg/
day
established
in
the
developmental
rabbit
study
was
compared
with
the
dermal
NOEL
of
1000
mg/
kg/
day
established
in
the
dermal
study
with
the
same
species
(
rabbits)
(
Oral
NOEL
=
24
mg/
kg/
day
/
Dermal
NOEL
=
1000
mg/
kg/
day
x
100
=
approximate
dermal
absorption
=
2.4%).

6)
In
addition,
if
there
is
no
systemic
toxicity
with
the
technical
material
which
was
used
in
the
toxicity
studies,
exposure
to
the
formulated
products
with
lower
technical
active
ingredients
even
lessens
the
risk
in
real­
life
situations.

7)
Domestic
animal
safety
studies
conducted
with
cats
and
dogs
following
single
or
repeated
dermal
applications
of
Imidacloprid
(
10%
formulation)
showed
no
major
treatment­
related
dermal,
clinical
signs,
body
weight
effects
or
clinical
chemistry
alterations.
These
studies
demonstrated
that
cats
and
dogs
can
tolerated
50
mg/
kg
without
significant
adverse
reactions
(
MRID
Nos.
43679501,
43679502,
43679607,
43679608).

Based
on
these
observations,
HIARC
re­
affirmed
their
earlier
conclusion
that
occupational/
residential
risk
assessments
are
not
required
for
dermal
exposures
to
Imidacloprid.
